Meiosis and sporulation in the eukaryotic yeast Saccharomyces cerevisiae can be initiated by the partial deprivation of purine nucelotides and most effectively by the deprivation of guanine nucleotides (GTP). This was shown by the use of specific auxotrophic mutants or by the addition of specific inhibitors of GMP synthesis, the most effective inducer being virazole (=ribavirin). The differentiation of yeast can also be caused by partial deprivation of sulfur or methionine, both of which result in a decrease of the intracellular concentration of S-adenosyl0methionine (SAM) as well as GTP. As GTP deprivation also produces a decrease in SAM, it is not clear which of the two compounds control sporulation. Experiments are underway to decide that. To determine which protein changes are involved in meiosis, a method has been developed to isolate large numbers of nuclei rapidly and cleanly. Two-dimensional electrophoresis was used to determine qualitative and quantiative changes in nuclear proteins.